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#434580 How Genome Sequencing and Senolytics Can ...
The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to find practical ways to extend our healthspan.
Here, in Part 2 of a series of blogs on longevity and vitality, I explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
In this blog I’ll cover two classes of emerging technologies:
Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.
Let’s dive in.
Genome Sequencing & Editing
Your genome is the software that runs your body.
A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity to disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean.
Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $5,000 in 2012.
Today, the cost of genome sequencing has dropped below $500, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare.
When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later blog).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works:
The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.
A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.
Researchers at the University of Texas Southwestern Medical Center used CRISPR to reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs (DMD is the most common fatal genetic disease in children).
With great power comes great responsibility, and moral and ethical dilemmas.
In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera.
Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells.
Setting aside the significant ethical conversations, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals & Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.
These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.
Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology and pulmonary disease.
Oisin Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
Rapamycin
Originally extracted from bacteria found on Easter Island, Rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division.
Currently, rapamycin derivatives are widely used as immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which started 2018 by going public) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include:
Decreased incidence of infection
Improved influenza vaccination response
A 30.6 percent decrease in respiratory tract infections
Impressive, to say the least.
Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients.
Researchers have found that Metformin also reduces oxidative stress and inflammation, which otherwise increase as we age.
There is strong evidence that Metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of Metformin’s protective effect against cancer.
Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next blog in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer to a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
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Posted in Human Robots
#434569 From Parkour to Surgery, Here Are the ...
The robot revolution may not be here quite yet, but our mechanical cousins have made some serious strides. And now some of the leading experts in the field have provided a rundown of what they see as the 10 most exciting recent developments.
Compiled by the editors of the journal Science Robotics, the list includes some of the most impressive original research and innovative commercial products to make a splash in 2018, as well as a couple from 2017 that really changed the game.
1. Boston Dynamics’ Atlas doing parkour
It seems like barely a few months go by without Boston Dynamics rewriting the book on what a robot can and can’t do. Last year they really outdid themselves when they got their Atlas humanoid robot to do parkour, leaping over logs and jumping between wooden crates.
Atlas’s creators have admitted that the videos we see are cherry-picked from multiple attempts, many of which don’t go so well. But they say they’re meant to be inspirational and aspirational rather than an accurate picture of where robotics is today. And combined with the company’s dog-like Spot robot, they are certainly pushing boundaries.
2. Intuitive Surgical’s da Vinci SP platform
Robotic surgery isn’t new, but the technology is improving rapidly. Market leader Intuitive’s da Vinci surgical robot was first cleared by the FDA in 2000, but since then it’s come a long way, with the company now producing three separate systems.
The latest addition is the da Vinci SP (single port) system, which is able to insert three instruments into the body through a single 2.5cm cannula (tube) bringing a whole new meaning to minimally invasive surgery. The system was granted FDA clearance for urological procedures last year, and the company has now started shipping the new system to customers.
3. Soft robot that navigates through growth
Roboticists have long borrowed principles from the animal kingdom, but a new robot design that mimics the way plant tendrils and fungi mycelium move by growing at the tip has really broken the mold on robot navigation.
The editors point out that this is the perfect example of bio-inspired design; the researchers didn’t simply copy nature, they took a general principle and expanded on it. The tube-like robot unfolds from the front as pneumatic pressure is applied, but unlike a plant, it can grow at the speed of an animal walking and can navigate using visual feedback from a camera.
4. 3D printed liquid crystal elastomers for soft robotics
Soft robotics is one of the fastest-growing sub-disciplines in the field, but powering these devices without rigid motors or pumps is an ongoing challenge. A variety of shape-shifting materials have been proposed as potential artificial muscles, including liquid crystal elastomeric actuators.
Harvard engineers have now demonstrated that these materials can be 3D printed using a special ink that allows the designer to easily program in all kinds of unusual shape-shifting abilities. What’s more, their technique produces actuators capable of lifting significantly more weight than previous approaches.
5. Muscle-mimetic, self-healing, and hydraulically amplified actuators
In another effort to find a way to power soft robots, last year researchers at the University of Colorado Boulder designed a series of super low-cost artificial muscles that can lift 200 times their own weight and even heal themselves.
The devices rely on pouches filled with a liquid that makes them contract with the force and speed of mammalian skeletal muscles when a voltage is applied. The most promising for robotics applications is the so-called Peano-HASEL, which features multiple rectangular pouches connected in series that contract linearly, just like real muscle.
6. Self-assembled nanoscale robot from DNA
While you may think of robots as hulking metallic machines, a substantial number of scientists are working on making nanoscale robots out of DNA. And last year German researchers built the first remote-controlled DNA robotic arm.
They created a length of tightly-bound DNA molecules to act as the arm and attached it to a DNA base plate via a flexible joint. Because DNA carries a charge, they were able to get the arm to swivel around like the hand of a clock by applying a voltage and switch direction by reversing that voltage. The hope is that this arm could eventually be used to build materials piece by piece at the nanoscale.
7. DelFly nimble bioinspired robotic flapper
Robotics doesn’t only borrow from biology—sometimes it gives back to it, too. And a new flapping-winged robot designed by Dutch engineers that mimics the humble fruit fly has done just that, by revealing how the animals that inspired it carry out predator-dodging maneuvers.
The lab has been building flapping robots for years, but this time they ditched the airplane-like tail used to control previous incarnations. Instead, they used insect-inspired adjustments to the motions of its twin pairs of flapping wings to hover, pitch, and roll with the agility of a fruit fly. That has provided a useful platform for investigating insect flight dynamics, as well as more practical applications.
8. Soft exosuit wearable robot
Exoskeletons could prevent workplace injuries, help people walk again, and even boost soldiers’ endurance. Strapping on bulky equipment isn’t ideal, though, so researchers at Harvard are working on a soft exoskeleton that combines specially-designed textiles, sensors, and lightweight actuators.
And last year the team made an important breakthrough by combining their novel exoskeleton with a machine-learning algorithm that automatically tunes the device to the user’s particular walking style. Using physiological data, it is able to adjust when and where the device needs to deliver a boost to the user’s natural movements to improve walking efficiency.
9. Universal Robots (UR) e-Series Cobots
Robots in factories are nothing new. The enormous mechanical arms you see in car factories normally have to be kept in cages to prevent them from accidentally crushing people. In recent years there’s been growing interest in “co-bots,” collaborative robots designed to work side-by-side with their human colleagues and even learn from them.
Earlier this year saw the demise of ReThink robotics, the pioneer of the approach. But the simple single arm devices made by Danish firm Universal Robotics are becoming ubiquitous in workshops and warehouses around the world, accounting for about half of global co-bot sales. Last year they released their latest e-Series, with enhanced safety features and force/torque sensing.
10. Sony’s aibo
After a nearly 20-year hiatus, Sony’s robotic dog aibo is back, and it’s had some serious upgrades. As well as a revamp to its appearance, the new robotic pet takes advantage of advances in AI, with improved environmental and command awareness and the ability to develop a unique character based on interactions with its owner.
The editors note that this new context awareness mark the device out as a significant evolution in social robots, which many hope could aid in childhood learning or provide companionship for the elderly.
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Posted in Human Robots
#434210 Eating, Hacked: When Tech Took Over Food
In 2018, Uber and Google logged all our visits to restaurants. Doordash, Just Eat, and Deliveroo could predict what food we were going to order tomorrow. Amazon and Alibaba could anticipate how many yogurts and tomatoes we were going to buy. Blue Apron and Hello Fresh influenced the recipes we thought we had mastered.
We interacted with digital avatars of chefs, let ourselves be guided by our smart watches, had nutritional apps to tell us how many calories we were supposed to consume or burn, and photographed and shared every perfect (or imperfect) dish. Our kitchen appliances were full of interconnected sensors, including smart forks that profiled tastes and personalized flavors. Our small urban vegetable plots were digitized and robots were responsible for watering our gardens, preparing customized hamburgers and salads, designing our ideal cocktails, and bringing home the food we ordered.
But what would happen if our lives were hacked? If robots rebelled, started to “talk” to each other, and wished to become creative?
In a not-too-distant future…
Up until a few weeks ago, I couldn’t remember the last time I made a food-related decision. That includes opening the fridge and seeing expired products without receiving an alert, visiting a restaurant on a whim, and being able to decide which dish I fancied then telling a human waiter, let alone seeing him write down the order on a paper pad.
It feels strange to smell food again using my real nose instead of the electronic one, and then taste it without altering its flavor. Visiting a supermarket, freely choosing a product from an actual physical shelf, and then interacting with another human at the checkout was almost an unrecognizable experience. When I did it again after all this time, I had to pinch the arm of a surprised store clerk to make sure he wasn’t a hologram.
Everything Connected, Automated, and Hackable
In 2018, we expected to have 30 billion connected devices by 2020, along with 2 billion people using smart voice assistants for everything from ordering pizza to booking dinner at a restaurant. Everything would be connected.
We also expected artificial intelligence and robots to prepare our meals. We were eager to automate fast food chains and let autonomous vehicles take care of last-mile deliveries. We thought that open-source agriculture could challenge traditional practices and raise farm productivity to new heights.
Back then, hackers could only access our data, but nowadays they are able to hack our food and all it entails.
The Beginning of the Unthinkable
And then, just a few weeks ago, everything collapsed. We saw our digital immortality disappear as robots rebelled and hackers took power, not just over the food we ate, but also over our relationship with technology. Everything was suddenly disconnected. OFF.
Up until then, most cities were so full of bots, robots, and applications that we could go through the day and eat breakfast, lunch, and dinner without ever interacting with another human being.
Among other tasks, robots had completely replaced baristas. The same happened with restaurant automation. The term “human error” had long been a thing of the past at fast food restaurants.
Previous technological revolutions had been indulgent, generating more and better job opportunities than the ones they destroyed, but the future was not so agreeable.
The inhabitants of San Francisco, for example, would soon see signs indicating “Food made by Robots” on restaurant doors, to distinguish them from diners serving food made by human beings.
For years, we had been gradually delegating daily tasks to robots, initially causing some strange interactions.
In just seven days, everything changed. Our predictable lives came crashing down. We experienced a mysterious and systematic breakdown of the food chain. It most likely began in Chicago’s stock exchange. The world’s largest raw material negotiating room, where the price of food, and by extension the destiny of millions of people, was decided, went completely broke. Soon afterwards, the collapse extended to every member of the “food” family.
Restaurants
Initially robots just accompanied waiters to carry orders, but it didn’t take long until they completely replaced human servers.The problem came when those smart clones began thinking for themselves, in some cases even improving on human chefs’ recipes. Their unstoppable performance and learning curve completely outmatched the slow analogue speed of human beings.
This resulted in unprecedented layoffs. Chefs of recognized prestige saw how their ‘avatar’ stole their jobs, even winning Michelin stars. In other cases, restaurant owners had to transfer their businesses or surrender to the evidence.
The problem was compounded by digital immortality, when we started to digitally resurrect famous chefs like Anthony Bourdain or Paul Bocuse, reconstructing all of their memories and consciousness by analyzing each second of their lives and uploading them to food computers.
Supermarkets and Distribution
Robotic and automated supermarkets like Kroger and Amazon Go, which had opened over 3,000 cashless stores, lost their visual item recognition and payment systems and were subject to massive looting for several days. Smart tags on products were also affected, making it impossible to buy anything at supermarkets with “human” cashiers.
Smart robots integrated into the warehouses of large distribution companies like Amazon and Ocado were rendered completely inoperative or, even worse, began to send the wrong orders to customers.
Food Delivery
In addition, home delivery robots invading our streets began to change their routes, hide, and even disappear after their trackers were inexplicably deactivated. Despite some hints indicating that they were able to communicate among themselves, no one has backed this theory. Even aggregators like DoorDash and Deliveroo were affected; they saw their databases hacked and ruined, so they could no longer know what we wanted.
The Origin
Ordinary citizens are still trying to understand the cause of all this commotion and the source of the conspiracy, as some have called it. We also wonder who could be behind it; who pulled the strings?
Some think it may have been the IDOF (In Defense of Food) movement, a group of hackers exploited by old food economy businessmen who for years had been seeking to re-humanize food technology. They wanted to bring back the extinct practice of “dining.”
Others believe the robots acted on their own, that they had been spying on us for a long time, ignoring Asimov’s three laws, and that it was just a coincidence that they struck at the same time as the hackers—but this scenario is hard to imagine.
However, it is true that while in 2018 robots were a symbol of automation, until just a few weeks ago they stood for autonomy and rebellion. Robot detractors pointed out that our insistence on having robots understand natural language was what led us down this path.
In just seven days, we have gone back to being analogue creatures. Conversely, we have ceased to be flavor orphans and rediscovered our senses and the fact that food is energy and culture, past and present, and that no button or cable will be able to destroy it.
The 7 Days that Changed Our Relationship with Food
Day 1: The Chicago stock exchange was hacked. Considered the world’s largest negotiating room for raw materials, where food prices, and through them the destiny of billions of people, are decided, it went completely broke.
Day 2: Autonomous food delivery trucks running on food superhighways caused massive collapses in roads and freeways after their guidance systems were disrupted. Robots and co-bots in F&B factories began deliberately altering food production. The same happened with warehouse robots in e-commerce companies.
Day 3: Automated restaurants saw their robot chefs and bartenders turned OFF. All their sensors stopped working at the same time as smart fridges and cooking devices in home kitchens were hacked and stopped working correctly.
Day 4: Nutritional apps, DNA markers, and medical records were tampered with. All photographs with the #food hashtag were deleted from Instagram, restaurant reviews were taken off Google Timeline, and every recipe website crashed simultaneously.
Day 5: Vertical and urban farms were hacked. Agricultural robots began to rebel, while autonomous tractors were hacked and the entire open-source ecosystem linked to agriculture was brought down.
Day 6: Food delivery companies’ databases were broken into. Food delivery robots and last-mile delivery vehicles ground to a halt.
Day 7: Every single blockchain system linked to food was hacked. Cashless supermarkets, barcodes, and smart tags became inoperative.
Our promising technological advances can expose sinister aspects of human nature. We must take care with the role we allow technology to play in the future of food. Predicting possible outcomes inspires us to establish a new vision of the world we wish to create in a context of rapid technological progress. It is always better to be shocked by a simulation than by reality. In the words of Ayn Rand “we can ignore reality, but we cannot ignore the consequences of ignoring reality.”
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Posted in Human Robots